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Fisetin alleviates sepsis-induced multiple organ dysfunction in mice via inhibiting p38 MAPK/MK2 signaling.

Abstract：

:Sepsis-induced multiple organ dysfunction and inflammatory response are life-threatening symptoms without effective treatment. Fisetin, a dietary flavonoid extracted from berries and family Fabaceae, has displayed neuroprotective and anti-oxidant activities. In this study we investigated whether fisetin exerted a protective effect against sepsis-induced multiple organ dysfunction in mouse cecum ligation and puncture (CLP) model. The mice were injected with fisetin (10 mg/kg, ip) 0.5 h prior to CLP, and sacrificed 18 h after CLP. We found that fisetin administration significantly alleviated CLP-induced lung, liver and kidney injury, as well as the expression levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-1β in bronchoalveolar lavage fluid (BALF). In lipopolysaccharide (LPS)-treated mouse bone marrow-derived macrophages (BMDMs), application of fisetin (3-10 μM) dose-dependently inhibited the expression levels of IL-6, TNF-α, IL-1β, and inducible nitric oxide synthase (iNOS). Furthermore, fisetin dose-dependently inhibited the phosphorylation of p38 MAPK, MK2, and transforming growth factor-β-activated kinase (TAK) 1 via attenuating the interaction between TAK1 and TAK-binding proteins (TAB) 1. These results demonstrate that fisetin is a promising agent for protecting against sepsis-induced inflammatory response and organ injury via inhibiting macrophage activation.

journal_name

Acta Pharmacol Sin

journal_title

Acta pharmacologica Sinica

authors

Zhang HF,Zhang HB,Wu XP,Guo YL,Cheng WD,Qian F

doi

10.1038/s41401-020-0462-y

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

1348-1356

issue

10

eissn

1671-4083

issn

1745-7254

pii

10.1038/s41401-020-0462-y

journal_volume

41

pub_type

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